The subject matter disclosed herein relates to generating genetically modified organisms and, in particular, to genetically modified organisms with an increased representation of odorant receptors, which concomitantly enhances the sense of smell. Currently, animals such as dogs, bees and rats are deployed to help humans with scent detection tasks, but their use is expensive since they require long-term training. Having a genetically manipulated organism with an increased representation of specific odorant receptors will considerably shorten the training process and advance animal-based scent detection tasks. Having a genetically manipulated organism with an increased representation of specific odorant receptors increases researcher's ability to analyze odors that activate that particular odorant receptors.
Volatile chemicals are detected by several million olfactory sensory neurons (OSNs) arrayed in a sensory epithelium located inside the nasal cavity. The main olfactory epithelium (MOE) expresses odorant receptors (ORs) through a poorly understood singular gene choice mechanism whereby only one allele of any OR gene is selected for specific expression in a given neuron. Typically, ˜0.1% of the total number of OSNs in the MOE expresses the same OR and their axons coalesce into homotypic glomeruli in the olfactory bulb, the first relay station for synaptic activity in the brain. Thus, all ORs being expressed in equal and low representation makes the olfactory neuronal sheet a broad, non-specific detector of odorants.
Several million olfactory sensory neurons (OSNs) in the nose are used to identify volatile chemicals (odors). Rodents and dogs carry about 1000 individual odorant receptor (OR) genes, whose proteins can bind to specific odors; roughly 10,000 neurons are associated with an individual OR gene. Thus, each OR is present in an equal and low representation (0.1%), which makes the olfactory neuronal sheet a broad, non-specific detector of odorants.
There has been limited success in odor profiling ORs expressed in heterologous cells in vitro. Part of this limitation is due to the inability of OR proteins to traffic to the plasma membrane. In addition, given the biological properties of the olfactory system many in vitro characterized OR alleles may not be functional in an in vivo setting. The major drawback, though, has been the ability to rapidly contrast how odors presented in liquid phase (in vitro) correspond to odors presented to the OR in vapor phase within their mucosal environment (in vivo). Even ex vivo patching of dendritic knobs from transgenic and gene-targeted mice suffers from an absence of vapor phase delivery of odors. In addition, the study of both OR gene choice and OR coding in vivo is hampered by the low representation of a given OR, i.e. only ˜0.1% on average of the total neuronal population in a wild type mouse. A rapid in vivo approach to odor profile any OR would be a breakthrough and permit researchers to correlate in vitro, ex vivo, and in vivo responses. Unfortunately, no suitable in vivo approach is known.
The discussion above is merely provided for general background information and is not intended to be used as an aid in determining the scope of the claimed subject matter.